A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors.
A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors.
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DOI：
10.15252/emmm.201707726
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发表时间：
2017-09
影响因子：
11.1
通讯作者：
Paulson JC
中科院分区：
文献类型：
--
作者：
de Vries RP;Tzarum N;Peng W;Thompson AJ;Ambepitiya Wickramasinghe IN;de la Pena ATT;van Breemen MJ;Bouwman KM;Zhu X;McBride R;Yu W;Sanders RW;Verheije MH;Wilson IA;Paulson JC
2013年6月，一名台湾妇女报告了首例人感染h5n1禽流感病毒病例。虽然这是一个单一的非致命病例，但该病毒继续在台湾家禽中传播。与任何感染人类的新出现的禽流感病毒一样，人们担心获得人型受体特异性可能使其在人群中传播。尽管人类H6N1分离物的受体结合袋发生突变，但它保留了鸟型（NeuAcα2‐3Gal）受体特异性。然而，我们在这里发现了一个单核苷酸替换，导致225位（G225D）从Gly变为Asp，完全改变了对人型（NeuAcα2‐6Gal）受体的特异性。值得注意的是，G225D H6失去了与鸡气管上皮的结合，现在能够与人气管组织结合。结构分析表明，Asp225直接与人型受体的倒数第二个Gal相互作用，稳定了人型受体的结合。
In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non‐fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human‐type receptor specificity could enable transmission in the human population. Despite mutations in the receptor‐binding pocket of the human H6N1 isolate, it has retained avian‐type (NeuAcα2‐3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human‐type (NeuAcα2‐6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human‐type receptor, stabilizing human receptor binding.
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影响因子：
64.5
作者：
Linster M;van Boheemen S;de Graaf M;Schrauwen EJA;Lexmond P;Mänz B;Bestebroer TM;Baumann J;van Riel D;Rimmelzwaan GF;Osterhaus ADME;Matrosovich M;Fouchier RAM;Herfst S
通讯作者：
Herfst S
影响因子：
3.7
作者：
Chen LM;Blixt O;Stevens J;Lipatov AS;Davis CT;Collins BE;Cox NJ;Paulson JC;Donis RO
通讯作者：
Donis RO
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
de Vries, Robert P.;Zhu, Xueyong;Paulson, James C.
通讯作者：
Paulson, James C.
影响因子：
3.7
作者：
de Vries, Robert P.;de Vries, Erik;de Haan, Cornelis A. M.
通讯作者：
de Haan, Cornelis A. M.